Biomatrix Scaffolds

a biomatrix and scaffold technology, applied in the field of biomatrix scaffolds, can solve the problems of major loss of some matrix components, inability to recapitulate the complex matrix chemistry and architecture of tissue, etc., and achieve the effects of good attachment, improved quality of cryopreserved cells, and higher levels of p450s

Active Publication Date: 2013-08-01
THE UNIV OF NORTH CAROLINA AT CHAPEL HILL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0047]The present invention is directed to the discovery and development of a biomatrix scaffold that has unexpected improvements and advantages over decellularized tissue scaffolds now known, some examples of the improvement and advantage being the use of the biomatrix scaffold of this invention to efficiently maintain mature cells and / or to lineage restrict and / or differentiate stem cells to mature fates and / or to maintain such matured cells as functional for an extended period of time. As a further example, use of the biomatrix scaffolds of this invention reduces the time to produce cells of mature fates from about three to six weeks or more to about one to two weeks. The biomatrix scaffolds of this invention are produced using specific protocols that employ the appropriate balance of salt concentration and ionic strength (different collagens have different solubility constants (23)) for a given tissue, to allow for the retention of native collagens present in that tissue in insoluble form, resulting in a biomatrix scaffold that retains a high percent of native collagens that provide signals to drive lineage restriction and differentiation. In contrast, decellularized scaffolds produced according to known protocols do not employ such a balance of salt concentration and ionic strength to allow for retention of a high percent of these native collagens and most of these native collagens are lost when these known protocols are used. Furthermore, the biomatrix scaffolds of this invention allow for production of lineage dependent (e.g., differentiation dependent) viruses and / or pathogens in amounts sufficient for experimental and / or therapeutic use (e.g., for vaccine production).

Problems solved by technology

However, individual matrix components, alone or in combination, are unable to recapitulate a tissue's complex matrix chemistry and architecture.
However, current decellularization protocols result in major losses of some of the matrix components due to the use of matrix-degrading enzymes or buffers that solubilize matrix components.

Method used

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Examples

Experimental program
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example 1

REFERENCES FOR EXAMPLE 1

[0187]1. Lanza, R. et al. Handbook of Stem Cells, Vol. 2 volumes. (Elsevier Academic Press, New York City; 2004).[0188]2. Vacanti, J. P. & Langer, R. Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 354 Suppl 1, SI32-34 (1999).[0189]3. * Schmelzer, E. et al. Human hepatic stem cells from fetal and postnatal donors. Journal of Experimental Medicine 204, 1973-1987 [*co-equal first authors; **co-equal senior authors] (2007).[0190]4. Zhang, L., Theise, N., Chua, M. & Reid, L. M. Human hepatic stem cells and hepatoblasts: Symmetry between Liver Development and Liver Regeneration. Hepatology 48, 1598-1607 (2008).[0191]5. Kubota, H. & Reid, L. M. Clonogenic hepatoblasts, common precursors for hepatocytic and biliary lineages, are lacking classical major histocompatibility complex class I antigens. Proceedings of the National Academy of Sciences of the United States of America 97, 121...

example 2

Use of Biomatrix Scaffolds for Cultures of Tumor Cell Lines or Primary Cultures of Tumors

[0239]The biomatrix scaffolds of this invention can be used for producing cultures of tumor cell lines or of primary cultures of tumors. The ability to do this means that a patient's tumor can be assessed for sensitivity to various therapies in an ex vivo assay.

[0240]The biomatrix scaffolds of this invention can also be used as substrata for grafts of tumors (whether syngeneic, allogeneic, or xenogenic) transplanted into hosts.

[0241]The biomatrix scaffolds of this invention can also be used to assess the metastatic potential of a tumor. Tumor cells are seeded at low cell densities onto substrata of biomatrix scaffolds from various tissues. The tumor cells will attach and survive on many types of biomatrix scaffolds. They will grow and form colonies preferentially on some of them. Their ability to form colonies on a specific type of biomatrix scaffold is predictive of the tumor cells' ability to ...

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Abstract

The present invention provides biomatrix scaffolds, a tissue extract enriched for extracellular matrix components and bound growth factors, cytokines and hormones, and methods of making and using same.

Description

STATEMENT OF PRIORITY[0001]This application claims the benefit, under 35 U.S.C. §119(e), of U.S. Provisional Application Ser. No. 61 / 360,939, filed Jul. 2, 2010, the entire contents of which are incorporated by reference herein.STATEMENT OF GOVERNMENT SUPPORT[0002]Aspects of this invention were made with government support under National Institutes of Health (NIH) Grant Nos. AA014243 and IP30-DK065933, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant No. DK34987, National Cancer Institute (NCI) Grant No. CA016086 and National Institute of Dental and Craniofacial Research No. DE019569. The United States Government has certain rights to this invention.FIELD OF THE INVENTION[0003]This invention concerns biomatrix scaffolds and methods of producing biomatrix scaffolds and their use in diverse applications as intact scaffolds or as scaffolds that are sectioned or pulverized and dispersed in various ways for specific experimental and clinical uses.BACKGROUND ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N5/00
CPCA61L27/3604A61L27/3683C12N5/0671C12N5/0068C12N2533/90A61L27/3691C12N5/067C12N5/0693C12N7/00C12N2770/24223C12N2770/24252C12N2730/10123C12N2730/10152C12N2710/20023C12N2710/20052A61L2430/28A61L27/24C12N2500/25C12N2500/36C12N2501/20C12N2501/998C12N2506/14C12N2533/54
Inventor WANG, YUNFANGRIED, LOLA CYNTHIA MCADAMSYAMAUCHI, MITSUOCUI, CAI-BINWANG, ANDREW ZHUANGWERNER, MICHAEL EDWARD
Owner THE UNIV OF NORTH CAROLINA AT CHAPEL HILL
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